Aldehydes and ketones are valuable building blocks for chemical industry. Reductive amination is a fundamental chemistry process that dramatically expands the application of aldehydes and ketones by transforming them into amines. The Leuckart reaction is a unique one step method of reductive amination. It is a remarkably simple process that includes only two components: the carbonyl compound and formamide. The reaction is completed simply by heating the components at 160° C. to 185° C. for 6 to 25 hours [1]. The long processing time seemed to be the only shortcoming of the reaction. However, it is associated with a number of serious practical problems.
First, the prolonged exposure of the reaction mixture to high temperatures inevitably leads to significant thermal decomposition of the components, and, consequently, to lower yields of the products and difficulties with their isolation and purification. Second, maintaining high temperatures for a long period of time means high consumption of energy and increasing production costs which make the Leuckart reaction unattractive to chemical industry. Third, long processing times per se are unattractive to fast paced modern synthetic applications, such as combinatorial chemistry and automated parallel synthesis. Thus, the Leuckart reaction as a unique one step method of reductive amination became almost completely abandoned in modern synthetic chemistry.
Most of the current reductive amination procedures are currently performed as two step combinations of the separate amination and reduction reactions. These two step procedures can often take as much time as the traditional Leuckart reaction [2]. They are also quite expensive because they require either the use of custom complex hydrides, or precious metal catalysts and high pressure equipment. Their only advantage over the one step Leuckart reaction is that they are not accompanied by thermal decomposition and as a result produce cleaner products.
Therefore, it is evident that there is a compelling need for a fast and inexpensive method of reductive amination of aldehydes and ketones equally attractive to industrial and laboratory practices.